Roberts syndrome (RS) is a recessively-inherited, developmental disorder characterized by symmetrical limb reductions, profound pre- and postnatal growth retardation and a number of craniofacial abnormalities including cleft lip and cleft palate. About half of these patients also have an unusual chromosome abnormality involving heterochromatin but have a normal karyotype when examined by conventional techniques. Dermal fibroblasts from 3 such patients have been shown to have a number of abnormal characteristics when grown in culture. These include decreased growth rates and plating efficiencies, premature senescence in culture, increased cell size, mitotic abnormalities and high death rates. They are also hypersensitive to certain mutagens. One set of experiments is designed to determine whether the proliferative defects seen in cells from these first cases will also be found in available strains derived from a larger population of such patients and whether the severity of the abnormalities varies between patients, perhaps in proportion to the severity of the syndrome. Whether or not these characteristics occur in heterozygous carriers will also be determined. A second set of experiments is designed to identify the metabolic, cellular and molecular bases of the syndrome and to eventually lead to the identification of the defective gene. These include nutrient supplementation studies, studies of nucleotide pools, an analysis of the ability of these cells to progress through the cell cycle and a study of their ability to synthesize RNA and protein using autoradiographic, flow cytometric and quantitative video intensification microscopic techniques. In addition to increasing our understanding of this syndrome, this work can serve as a model for the study of proliferation defects in other malformation/growth-retardation syndromes and in experimental systems used to study the mechanism of action of teratogenic agents.